Xcopri vs. Keppra: A head-to-head analysis
For adults living with epilepsy, managing focal onset seizures is a primary treatment goal. Two key medications often considered are Xcopri (cenobamate) and Keppra (levetiracetam), both effective anticonvulsants with distinct profiles. However, their differences in mechanism of action, side effects, cost, and usage protocols mean that one may be a more suitable choice than the other depending on individual patient needs. This article provides a comprehensive comparison to help understand the factors involved in deciding if Xcopri is better than Keppra for a particular situation.
Understanding Xcopri and Keppra
Xcopri (cenobamate)
Approved by the FDA in 2019, Xcopri is a newer anti-seizure medication (ASM) specifically for treating partial-onset (focal) seizures in adults. It features a dual mechanism of action, which is thought to contribute to its high efficacy, especially in patients with drug-resistant seizures. Xcopri acts as a positive allosteric modulator of the GABA-A receptor and also inhibits the persistent sodium current, helping to prevent seizure initiation and spread. It is a once-daily oral tablet, but requires a slow, gradual titration period of several weeks to reduce the risk of serious side effects, such as the potentially fatal Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). A significant difference is that Xcopri is classified as a Schedule V controlled substance due to a potential for abuse and dependence.
Keppra (levetiracetam)
Keppra has been available for much longer, having received FDA approval in 1999. It is approved for a wider range of seizure types and age groups than Xcopri, including focal onset, myoclonic, and tonic-clonic seizures in both adults and children. Keppra's mechanism of action is distinct, involving binding to the synaptic vesicle protein 2A (SV2A), which modulates neurotransmitter release to reduce seizure activity. It is available in various forms, including immediate-release tablets, extended-release tablets (Keppra XR), an oral solution, and an intravenous (IV) solution. A major advantage is the availability of generic levetiracetam, which makes it a much more affordable option. Unlike Xcopri, Keppra is not a controlled substance.
Comparison of key factors
| Feature | Xcopri (cenobamate) | Keppra (levetiracetam) |
|---|---|---|
| Primary Indication | Focal onset seizures in adults | Focal onset seizures (adults & children), Myoclonic seizures, Tonic-clonic seizures |
| Efficacy | Potentially higher for drug-resistant focal seizures, high rate of seizure freedom reported in studies | Very effective, often used as a first-line treatment; some patients may develop tolerance over time |
| Mechanism of Action | Dual mechanism: Positive GABA-A modulator & sodium channel blocker | Binds to synaptic vesicle protein 2A (SV2A) |
| Side Effects (Common) | Dizziness, somnolence, fatigue, headache, double vision | Sleepiness, dizziness, aggression, irritability, mood swings |
| Side Effects (Serious) | DRESS, QT shortening, suicidal ideation | Suicidal ideation, Stevens-Johnson syndrome (SJS) |
| Cost | Brand-name only; generally very expensive | Generic levetiracetam available; typically much less expensive |
| Dosing Schedule | Once daily, after a slow titration period | Twice daily for immediate-release; once daily for extended-release (XR) |
| Controlled Substance | Yes, Schedule V | No |
| Pediatric Use | No, for adults only | Yes, approved for some seizures in children as young as 1 month |
Effectiveness for drug-resistant epilepsy
For patients whose seizures have not been adequately controlled by other medications, Xcopri offers a promising new avenue. Its distinct dual mechanism of action allows it to work differently than many other ASMs, potentially succeeding where others have failed. Clinical trials demonstrated significant seizure frequency reduction and even seizure-free periods in a notable percentage of patients, particularly during the maintenance phase. This is a key reason why a physician might transition a patient to Xcopri if Keppra, or other treatments, have proven insufficient. Keppra, while a highly effective and widespread treatment, is known to have some patients develop tolerance over time, leading to reduced efficacy.
Tolerability and side effects
While Xcopri and Keppra share some common side effects, such as dizziness and drowsiness, patient tolerance is a crucial differentiating factor. Keppra is famously associated with neuropsychiatric side effects, often dubbed "Keppra rage," including aggression, irritability, and mood swings. These behavioral changes can be difficult to manage and may be a reason for discontinuing the medication. Xcopri, in contrast, may be better tolerated in this regard for some individuals, though it has its own unique risks.
Xcopri requires a very slow dose titration to minimize the risk of DRESS, a severe skin and organ reaction. It also carries a risk of QT shortening, a type of irregular heart rhythm that is not associated with Keppra. The side effect profile must be carefully weighed by the prescribing physician, taking into account the patient's full medical history.
Cost and access
Cost and accessibility are major considerations. As a newer, brand-name-only medication, Xcopri is significantly more expensive than Keppra, which has widely available and affordable generic versions. While insurance coverage varies, the out-of-pocket costs for Xcopri can be a barrier for many patients. This makes generic levetiracetam (Keppra) the more accessible and cost-effective option for most people, especially as a first-line treatment.
Conclusion
Determining if Xcopri is better than Keppra depends entirely on the individual's clinical situation. For patients with well-controlled seizures or those seeking a more affordable, broadly approved medication, Keppra (or its generic, levetiracetam) remains an excellent standard of care. Its extensive track record and availability make it a reliable choice. However, for adults who have drug-resistant focal seizures and have not found success with other treatments, Xcopri's superior efficacy and novel mechanism of action present a powerful alternative, despite the higher cost, stricter titration, and different side effect profile. Ultimately, the choice between these medications should be a collaborative decision between a patient and their neurologist, based on efficacy, tolerability, cost, and specific seizure characteristics.
For more detailed prescribing information on both medications, please refer to the FDA website.
Xcopri vs. Keppra: A head-to-head analysis
For adults living with epilepsy, managing focal onset seizures is a primary treatment goal. Two key medications often considered are Xcopri (cenobamate) and Keppra (levetiracetam), both effective anticonvulsants with distinct profiles. However, their differences in mechanism of action, side effects, cost, and usage protocols mean that one may be a more suitable choice than the other depending on individual patient needs. This article provides a comprehensive comparison to help understand the factors involved in deciding if Xcopri is better than Keppra for a particular situation.
Understanding Xcopri and Keppra
Xcopri (cenobamate)
Approved by the FDA in 2019, Xcopri is a newer anti-seizure medication (ASM) specifically for treating partial-onset (focal) seizures in adults. It features a dual mechanism of action, which is thought to contribute to its high efficacy, especially in patients with drug-resistant seizures. Xcopri acts as a positive allosteric modulator of the GABA-A receptor and also inhibits the persistent sodium current, helping to prevent seizure initiation and spread. It is a once-daily oral tablet, but requires a slow, gradual titration period of several weeks to reduce the risk of serious side effects, such as the potentially fatal Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). A significant difference is that Xcopri is classified as a Schedule V controlled substance due to a potential for abuse and dependence.
Keppra (levetiracetam)
Keppra has been available for much longer, having received FDA approval in 1999. It is approved for a wider range of seizure types and age groups than Xcopri, including focal onset, myoclonic, and tonic-clonic seizures in both adults and children. Keppra's mechanism of action is distinct, involving binding to the synaptic vesicle protein 2A (SV2A), which modulates neurotransmitter release to reduce seizure activity. It is available in various forms, including immediate-release tablets, extended-release tablets (Keppra XR), an oral solution, and an intravenous (IV) solution. A major advantage is the availability of generic levetiracetam, which makes it a much more affordable option. Unlike Xcopri, Keppra is not a controlled substance.
Comparison of key factors
| Feature | Xcopri (cenobamate) | Keppra (levetiracetam) |
|---|---|---|
| Primary Indication | Focal onset seizures in adults | Focal onset seizures (adults & children), Myoclonic seizures, Tonic-clonic seizures |
| Efficacy | Potentially higher for drug-resistant focal seizures, high rate of seizure freedom reported in studies | Very effective, often used as a first-line treatment; some patients may develop tolerance over time |
| Mechanism of Action | Dual mechanism: Positive GABA-A modulator & sodium channel blocker | Binds to synaptic vesicle protein 2A (SV2A) |
| Side Effects (Common) | Dizziness, somnolence, fatigue, headache, double vision | Sleepiness, dizziness, aggression, irritability, mood swings |
| Side Effects (Serious) | DRESS, QT shortening, suicidal ideation | Suicidal ideation, Stevens-Johnson syndrome (SJS) |
| Cost | Brand-name only; generally very expensive | Generic levetiracetam available; typically much less expensive |
| Dosing Schedule | Once daily, after a slow titration period | Twice daily for immediate-release; once daily for extended-release (XR) |
| Controlled Substance | Yes, Schedule V | No |
| Pediatric Use | No, for adults only | Yes, approved for some seizures in children as young as 1 month |
Effectiveness for drug-resistant epilepsy
For patients whose seizures have not been adequately controlled by other medications, Xcopri offers a promising new avenue. Its distinct dual mechanism of action allows it to work differently than many other ASMs, potentially succeeding where others have failed. Clinical trials demonstrated significant seizure frequency reduction and even seizure-free periods in a notable percentage of patients, particularly during the maintenance phase. This is a key reason why a physician might transition a patient to Xcopri if Keppra, or other treatments, have proven insufficient. Keppra, while a highly effective and widespread treatment, is known to have some patients develop tolerance over time, leading to reduced efficacy.
Tolerability and side effects
While Xcopri and Keppra share some common side effects, such as dizziness and drowsiness, patient tolerance is a crucial differentiating factor. Keppra is famously associated with neuropsychiatric side effects, often dubbed "Keppra rage," including aggression, irritability, and mood swings. These behavioral changes can be difficult to manage and may be a reason for discontinuing the medication. Xcopri, in contrast, may be better tolerated in this regard for some individuals, though it has its own unique risks.
Xcopri requires a very slow dose titration to minimize the risk of DRESS, a severe skin and organ reaction. It also carries a risk of QT shortening, a type of irregular heart rhythm that is not associated with Keppra. The side effect profile must be carefully weighed by the prescribing physician, taking into account the patient's full medical history.
Cost and access
Cost and accessibility are major considerations. As a newer, brand-name-only medication, Xcopri is significantly more expensive than Keppra, which has widely available and affordable generic versions. While insurance coverage varies, the out-of-pocket costs for Xcopri can be a barrier for many patients. This makes generic levetiracetam (Keppra) the more accessible and cost-effective option for most people, especially as a first-line treatment.
Conclusion
Determining if Xcopri is better than Keppra depends entirely on the individual's clinical situation. For patients with well-controlled seizures or those seeking a more affordable, broadly approved medication, Keppra (or its generic, levetiracetam) remains an excellent standard of care. Its extensive track record and availability make it a reliable choice. However, for adults who have drug-resistant focal seizures and have not found success with other treatments, Xcopri's superior efficacy and novel mechanism of action present a powerful alternative, despite the higher cost, stricter titration, and different side effect profile. Ultimately, the choice between these medications should be a collaborative decision between a patient and their neurologist, based on efficacy, tolerability, cost, and specific seizure characteristics.
For more detailed prescribing information on both medications, please refer to the FDA website.
